Progressive telomere shortening occurs with the division of normal human cells. Once telomeres become sufficiently short, they trigger cellular sensescence. However, the mechanism by which the shortened the shortened telomeres cause permanent growth arrest remains to be explored.. Transcriptional repression of genes adjacent to telomeres is a well-documented phenomenon in yeast, but only one study, involving the introduction of a exogenous reporter gene, reported a similar observation in human cells. Recent completion of the human genome project and identification of expressed sequences at subtelomeric regions has made it possible to study the endogenous subtelomeric genes.. We propose to take a microarray approach to test the hypothesis that telomere length and subtelomeric heterochromatin structure regulates subtelomeric gene expression. We will analyze subtelomeric gene expression profiles of senescent and young cells on a genome-wide scan. After identifying subtelomeric gene that are highly expressed in senescent cells, we will further characterize these genes and introduce these genes, using an inducible expression system, into young cells to determine their roles in cellular senescence and cell growth regulation.